Figure 7: SSBP1 regulates nuclear H₂O₂ levels and mediates cisplatin resistance in ovarian cancer cells.

(A) SSBP1 depletion decreases nuclear H₂O₂ levels following treatment with anticancer agents in K562 cells. (B) Comparison of fold-change in nuclear H₂O₂ levels with proliferation rescue in K562 cells depleted of SSBP1 following treatment with the indicated compounds. (C) Lower SSBP1 levels correlate with shorter platinum free intervals (PFI) in high-grade serous ovarian cancer (HGSOC) tumors. (D) SSPB1 levels are decreased in platinum-refractory HGSOC tumors. (E) Knockdown of SSBP1 decreases cisplatin regulated nuclear H₂O₂ levels in ovarian cancer cell lines. (F) Heatmap depicting fold change in DDP IC₅₀ values in ovarian cancer cell lines expressing the indicated shRNAs targeting SSBP1. (G-H) DDP-resistant ovarian cancers have decreased SSBP1 expression. (G) DDP IC₅₀ values were measured in parental or DDP-resistant ovarian cancer cell lines. (H) Immunoblot analysis of SSBP1 in the indicated cell lines. (I) Model. Nuclear H₂O₂ activates CHK1 leading to the phosphorylation and cytosolic retention of SSBP1. Cytosolic SSBP1 cannot promote mitochondrial translation which generates H₂O₂. Mitochondrial H₂O₂ is transmitted to the nucleus following a decrease in GSH:GSSH ratio by certain anticancer drugs. Data are represented as mean ± SEM. * p < 0.05, ***p< 0.0001. Statistical significance was determined by one-way ANOVA with Sidak’s post-hoc correction.